P507: SALVAGE THERAPY WITH VENETOCLAX IN COMBINATION WITH AZACITIDINE, HOMOHARRINGTONINE AND CYTARABINE IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA
Authors: Linyu Yuan, Suo Xiaohui, Guanchen Bai, Hong LI, Zhongjing Han, Congcong Zhang, Yinling LI, Sifeng Gao, Jilei Zhang, Xinxiao Lu, Kaiqi Liu, Zhao Xingli
Journal: HemaSphere (2023)

Background: In recent years, the efficacy of acute myeloid leukemia (AML) has been improved, but the outcome of relapsed/refractory (R/R) AML patients is still poor. Traditional chemotherapy is not effective for these patients with complete remission(CR) 40-60%. Previous reports have shown that the combined application of some small-molecule targeted drugs (gilteritinib, enasidenib, ivosidenib, venetoclax, etc) could improve the therapeutic effect. Venetoclax (Ven), an oral Bcl-2 inhibitor, combined with azacitidine (AZA), decitabine and cytarabine (Ara-c) are effective in the treatment of newly diagnosed AML patients who are not eligible for intense chemotherapy, and the above regimen has also achieved good efficacy in the R/R AML with overall response rate (ORR) 21% to 75% and a median overall survival (OS) of 3-7.8 month. Previous research has shown that Homoharringtonine (HHT) and Ven can play a synergistic role in promoting tumor cell apoptosis through various pathways, and effectively cover the Ven resistance pathway. So that, Ven combined with AZA, HHT and Ara-c may improve the response rate in patients with R/R AML. Aims: Herein, we reported the data of 32 patients with R/R AML who were administered Ven+AZA+HHT+Ara-c as salvage therapy. The purpose of this study was to evaluate the efficacy and safety of this salvage regimen. Methods: Between Oct 2020 and Jan 2023, 32 patients with R/R AML were treated with this salvage regimen at 5 hospitals in China. The salvage therapy involved Ven (200mg/d, days 1-11, with dose adjustment in patients who also received azole antifungals), AZA (100 mg/d, days 2-8), HHT (2mg/m2/d, days 3-7) and Ara-c (100mg/d, days 3-9). Patients with FLT3-ITD mutations, allowing added sorafenib 600mg-800mg on days 4-10. The primary objective was ORR (including complete response (CR) + complete response without haematological recovery (CRi) + partial response (PR)), Secondary objectives were bone marrow minimal residual disease (MRD) by flow cytometry after one cycle of salvage treatment, OS and safety. Results: 32 patients were enrolled from Oct 2020 to Jan 2023. 62.5% （20/32） patients were men. The median age was 50（24-65）years old. Median number of prior lines of therapy was 1 (1-8), 5 patients (15.6%) who had undergone prior therapy with venetoclax. The ORR after one cycle salvage treatment was 68.8% with composite complete response rate (CR+CRi) 65.7%. 63.2% (12/19) patients who reached CR/CRi with undetectable MRD by flow cytometry. The ORR of patients who had previously received Ven was 80% (4/5). Untill Feb 2023, the estimated 1-years OS was 57.8%. Grade 3 or 4 anaemia, neutropenia and thrombocytopenia were the most common haematological adverse events during the salvage treatment and were presented in all enrolled patients. The most common non-hematologic adverse events were febrile neutropenia. 1 patient died during the therapy. Conclusion: Ven combined with AZA, HHT and Ara-c is a highly effective and safe salvage therapy for patients with R/R AML. Table 1. Patients Demographic and Baseline Characteristics, N=32 - Characteristic No. of Patients (%)or Median [Range] Gender Male 20 (62.5%) Female 12 (37.5%) Median age, years (range) 50 (24-65) ECOG performance status 0-1 27 (84.4%) ≥2 5 (15.6%) ELN 2022 risk group at the initial diagnosis Favorable 5 (15.6%) Intermediate 14 (43.7%) Adverse 10 (31.3%) Not Evaluable 3 (9.4%) ELN 2017 risk group at the initial diagnosis Favorable 6 (18.8%) Intermediate 15 (46.9%) Adverse 8 (25%) Not Evaluable 3 (9.4%) Molecular mutational panel at the initial diagnosis FLT3-ITD 10 (31.3%) ASXL1 4 (12.5%) IDH1/2 6 (18.8%) NPM1 6 (18.8%) Prior lines of therapy, median (range) 1 (1-8) Prior lines of therapy 1 20 (62.5%) ≥2 12 (37.5%) Prior therapy with venetoclax 5 (15.6%) Keywords: Venetoclax, Salvage therapy, Acute myeloid leukemia, relapsed/refractory